Targeting initiation of dose confirmation trial by end of 2021 with data readout by end of 2022 Initiation of Phase 3 pivotal trial targeted by mid-2023, with data readout and BLA filing targeted by end of 2024
Freeline Therapeutics Holdings plc (Nasdaq: FRLN) (the “Company” or “Freeline”) a clinical-stage biotechnology company developing transformative adeno-associated virus (“AAV”) vector-mediated gene therapies for patients suffering from inherited systemic debilitating diseases, today announced a modification to the clinical development plan for its FLT180a program for Hemophilia B.
The modification to the FLT180a clinical development plan is intended to address feedback Freeline received from the U.S. Food and Drug Administration (“FDA”) relating to the characterization and comparability of the investigational drug product used in its Phase 1/2 B-AMAZE trial that was produced at smaller scale, as compared to its current investigational drug product that is produced at commercial scale.
Under the modified clinical development plan, Freeline now plans to conduct dose confirmation in a FLT180a Phase 1/2 trial instead of in the Phase 2b part of the previously planned Phase 2b/3 pivotal trial. Freeline believes this modified clinical development plan should enable it to meet its objectives of initiating the clinical trial sites for the dose confirmation trial by the end of 2021, while in parallel, working to meet FDA’s Chemistry, Manufacturing and Control (“CMC”) requirements in advance of commencing the planned Phase 3 pivotal trial. The Company is targeting a data readout for the Phase 1/2 dose confirmation trial by the end of 2022, initiation of the Phase 3 pivotal trial by the middle of 2023 and filing of a Biologic License Application (“BLA”) with the FDA by the end of 2024.
The Company expects that the Phase 1/2 dose confirmation trial will be a six-month single dose safety and efficacy trial designed to confirm the dose and immune management regimen for the planned Phase 3 pivotal trial, with costs similar to those of the dose confirmation part of the previously planned Phase 2b/3 pivotal trial. Informed by the results of the dose-ranging B-AMAZE trial, which demonstrated a dose response across four cohorts, the Company believes that a dose of FLT180a between 7.5e11 and 9.75e11 vg/kg1 is likely to bring patients into the normal range of Factor IX (“FIX”) activity level of 50-150%.
The Company anticipates that the design of the Phase 3 pivotal trial will be nearly identical to the Phase 3 part of the previously planned Phase 2b/3 pivotal trial. Assuming the Phase 3 pivotal trial demonstrates robust data at 26 weeks, the Company believes it would be able to file a BLA with the FDA by the end of 2024 utilizing the Accelerated Approval pathway. The Company anticipates that the BLA filing would be based on the surrogate endpoint of FIX activity in approximately 20 patients, combined with demonstration of a positive correlation between 26-week FIX activity levels and 52-week annualized bleeding rates (“ABR”) in a subset of these 20 patients. The Phase 3 pivotal trial would continue to enroll up to an additional 30 patients to evaluate 52-week ABR to support full regulatory approval.
“We believe conducting dose confirmation in a Phase 1/2 trial should allow us to achieve similar objectives as our previously planned trial, whilst also enabling us to work with FDA on CMC prior to initiating the Phase 3 pivotal trial. We are still targeting the filing of our FLT180a BLA in 2024 and are committed to bringing a functional cure to Hemophilia B patients as soon as possible,” said Theresa Heggie, Chief Executive Officer of Freeline. “To streamline the development path for our subsequent programs, we have developed our entire pipeline from Phase 1 onward using the same commercial-scale manufacturing platform that we are now using for FLT180a.”